The present invention is directed to the field of ophthalmic and otic drug delivery. More specifically, the present invention is directed to the use of synthetic, inorganic nanoparticles as inert carriers for ophthalmic and otic drugs, and to the use of pharmaceutical compositions based on the invention to deliver ophthalmic drugs topically to the eye and ear.
Many different types of agents have been utilized as carriers for delivering ophthalmic drugs to the eye. For example, the use of carboxyvinyl polymers for this purpose is described in U.S. Pat. No. 4,271,143. Various other organic polymers have also been utilized as carriers for ophthalmic drugs.
The use of nanoparticles formed from synthetic or natural polymers in ophthalmic compositions has been described in various scientific publications, such as:    Kreuter, J. “Nanoparticles” Colloidal Drug Delivery Systems, edited by Jork Kreuter, Marcel Dekker, New York, N.Y. (USA), chapter 5, page 219 (1994);    Gurny, R. “Ocular therapy with nanoparticles” Polymeric Nanoparticles and Microspheres edited by P. Guiot and P. Couvreur, Boca Raton, Fla. (USA): CRC Press, page 127 (1986);    Gurny, R. “Preliminary study of prolonged acting drug delivery system for the treatment of glaucoma” Pharm Acta Helv., volume 56, page 130 (1981);    Zimmer, et al. “J. Microspheres and nanoparticles used in ocular delivery systems” Advanced Drug Delivery Reviews, volume 16, number 1, pages 61-73 (1995); and    Calvo, et al. “Comparative in vitro evaluation of several colloidal systems, nanoparticles, nanocapsules, and nanoemulsions, as ocular drug carriers” J Pharm Sci, volume 85, number 5. pages 530-536 (May 1996).
The nanoparticles utilized in the present invention are not formed from synthetic or natural polymers such as those described in the above-cited publications. Rather, the present invention is directed to the use of inorganic nanoparticles. The nanoparticles utilized in the present invention include, for example, clay substances that are water swellable. An extensive review of clays and their chemical and physical properties can be found in:    Giese, R. F. and van Oss C. J., “Colloid and Surface Properties of Clays and Related Minerals”, A. T. Hubbard, Marcel Dekker Inc., Vol. 105.
The preferred nanoparticles are formed from synthetic smectite clays which are prepared from simple silicates. The following publications may be referred to for further background regarding the use of synthetic clay nanoparticles in pharmaceutical compositions:    Plaizier-Vercammen, “Rheological properties of Laponite XLG, a synthetic purified hectorite” Pharmazie, volume 47, page 856 (1992);    Grandolini, et al. “Intercalation compounds of hydrotalcite-like anionic clays with anti-inflammatory agents: I. Intercalation and in vitro release of ibuprofen” International Journal of Pharmaceutics, volume 220, numbers 1-2, pages 23-32 (Jun. 4, 2001);
U.S. Pat. No. 5,585,108 (Ruddy, et al.) entitled “Formulations of Oral Gastrointestinal Therapeutic Agents in Combination with Pharmaceutically Acceptable Clays”;
U.S. Pat. No. 6,177,480 B1 (Tsuzuki, et al.), which describes the use of a synthetic clay material (i.e., Laponite™) as a wetting agent for contact lenses and to assist in the removal of lipid deposits from contact lenses by surfactants;
U.S. Pat. No. 6,015,816 (Kostyniak, et al.), which describes an improved method using colloid particles, such as smectite clay minerals, as a substrate for ligands having antimicrobial activity, so as to control microbial growth on a material; and
U.S. Pat. No. 6,177,480 (Tsuzuki, et al.) describes the use of synthetic clay material (i.e., Laponite™) as a wetting agent for contact lenses and to assist in the removal of lipid deposits from contact lenses by surfactants.